Our objective is to outline the cellular and molecular mechanisms involved in the regulation of expression of alkaline phosphatase in cell lines. Two reference HeLa cell lines, TCRC-1 and TCRC-2, provide model systems, monophenotypic for Regan and non-Regan isoenzymes. It is now possible then to study the influence of a variety of environmental factors including the separate addition to the medium of butyrate and of prednisolone. The non-Regan isoenzyme is equivalent to the early trophoblast form of alkaline phosphatase. In addition work will be continued on the modulation of isoenzyme expression of amnion-FL cells growing in tissue culture and in nude athymic mice. The identification of three developmental isoenzymes of alkaline phosphatase supplies a means of interpreting their variations in cell culture in terms of activation and de-activation of stage-specific developmental genes.